Provisional Designation of the Interleukin-6 Receptor (IL-6R) as a Novel Marker Gene for Exercise Tolerance

Objectives: Genomic markers linked to exercise-associated health benefits and/or sporting performance are increasingly used to guide decision-making in healthcare and sport/exercise science. This project investigated whether the IL-6R SNP “rs2228145” might be provisionally designated a novel physical activity/exercise marker. rs2228145 results in an Aspartate358/Alanine358 change adjacent to the site where the IL-6R protein is cleaved into two fragments, resulting in ~two-fold increases in bloodborne levels of soluble IL-6R [‘sIL-6R’]. Methods: Cohorts of staff/students at Cardiff Metropolitan University donated/completed: [i] finger-prick capillary blood samples (subjected to ELISAs for sIL-6R, the associated signalling protein sgp130, and the IL-6/sIL-6R complex); [ii] cheek-swab samples containing buccal epithelial cell DNA (subjected to PCR-based IL-6R/rs2228145 genotyping assays); [iii] International Physical Activity Questionnaires (to estimate physical activity levels in the week preceding sample donation). Results: As expected, we observed significant genotype-dependent differences in blood-borne sIL6R levels (CC (44.1±21.7ng/mL) vs. AC (28.6±7.3ng/mL) vs. AA (19.9±6.5ng/mL; P<0.05)); Importantly, AA homozygotes undertook significantly more physical activity than AC heterozygotes (6318±899 v. 3904±2280 MET-mins/week; P<0.01). Genotype was significantly associated with physical activity levels (P<0.05), and sIL-6R (P=0.197) and sgp130 (P=0.160) showed non-significant correlations with physical activity levels. Conclusions: These data suggest that IL-6R/rs2228145 genotype may influence participation in physical activity/exercise, perhaps by impacting on abilities to tolerate activity without experiencing adverse-effects. Although more research is required to confirm these preliminary findings, designation of IL-6R/ rs2228145 as a novel marker, and determination of participants’ IL-6R/rs2228145 genotypes, may in future be useful tools to aid exercise-providers in designing personalised exercise programmes matched to clients/patients.